title: Aptamer identification of brain tumor-initiating cells.
abstract: Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeutic resistance, tumor spread, and angiogenesis. The identification of TICs has been informed by the use of markers characterized in normal stem cells, but this approach has an inherent limitation to selectively identify TICs. To develop reagents that enrich TICs but not matched non-TICs or tissue-specific stem cells, we adopted Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic acid probes-aptamers-that specifically bind TICs. In this study, using Cell-SELEX with positive selection for TICs and negative selection for non-TICs and human neural progenitor cells, we identified TIC aptamers that specifically bind to TICs with excellent dissociation constants (Kd). These aptamers select and internalize into glioblastoma cells that self-renew, proliferate, and initiate tumors. As aptamers can be modified to deliver payloads, aptamers may represent novel agents that could selectively target or facilitate imaging of TICs.
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NE3-301, Cleveland, OH 44195, USA.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Wu
authors.forename: Petra
authors.initials: P
authors.lastname: Hamerlik
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hitomi
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Patrick
authors.initials: P
authors.lastname: Leahy
authors.forename: Anita B
authors.initials: AB
authors.lastname: Hjelmeland
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology*; D052156:SELEX Aptamer Technique / Q000379:methods*; D023041:Xenograft Model Antitumor Assays